This application relates to a method of providing androgen therapy to human male patients. More particularly, the application relates to a method of providing androgen supplementation without inducing an abnormal weight gain in the prostate.
In men, the prostate progressively enlarges throughout life. In some individuals obstruction of the urethra occurs so that the bladder will not empty efficiently. Surgery is often required to remove the portion of the prostate that obstructs the outflow of urine. Although not all of the factors which promote the continued growth of the prostate are understood, it is clear that prostate growth does not occur in the absence of testosterone, the major androgen secreted by the testes. Therefore, in men who need androgen replacement therapy, an approach which would minimize androgen delivery to the prostate cell could lessen the need for prostate surgery.
Androgen therapy in the human male has been used to treat sexual impotence and infertility, to induce sexual maturation at time of expected puberty and to maintain secondary sexual characteristics- Androgen therapy can also be used as a component of a male contraceptive. With the exception of contraception, these diverse conditions are in general manifestations of defective testicular function either primary or secondary, which results in insufficient testosterone production. As such, they are effectively treated by administration of an androgenic hormone such as testosterone.
Testosterone and its esters, e.g. testosterone enanthate and caproate, that are commonly used to treat androgen deficiency are not particularly potent androgens. As a consequence, 200 mg per month or more must be administered to achieve the desired level of activity. Since such a dose increases the risk of adverse side effects, a large number of testosterone analogs have been developed and tested for androgenic activity (see, e.g. Liao et al. J. Biol. Chem. 248, 6154-6162 (1973)), and many have been found to possess superior activity. These "super androgens" can therefore be used at much lower dosage levels than the natural androgen testosterone.
Merely being able to reduce the dosage level does not overcome all of the potential problems associated with testosterone therapy. This is because testosterone does not interact with all body tissues equally. Testosterone is converted in some tissues, notably the prostate, seminal vesicles, epididymides, and skin to 5.alpha.-dihydrotestosterone (DHT) which serves as the intracellular androgen in these organs. In contrast, in most other tissues of the body such as the brain, pituitary, muscle, kidney, etc. testosterone per se is the active intercellular androgen and it is not converted to DHT when testosterone is administered at a dose that will maintain libido (action on the brain) and anabolic activity (action on muscles).
Since DHT is a much more potent androgen than testosterone the effects of testosterone are amplified in tissues where DHT is produced. Thus, the prostate is provided with an unnecessarily high dose of androgen in the form of DHT when maintenance levels of testosterone are present. The resulting stimulation of prostate can cause unnecessary growth leading eventually to a potential need for prostate surgery. This amplification of an administered steroid, by way of its conversion to a more potent product, has also been observed for some of the more potent androgens. Thus, the administration of a lower dose of one of the potent androgens does not necessarily solve this problem associated with androgen therapy.